The effects of zucchini yellow mosaic virus (ZYMV) infection and pretreatments with salicylic acid (SA) on biomass accumulation of pumpkin (Cucurbita pepo cv. Eskandarani) were investigated. The response of photosynthesis, transpiration and the activities of antioxidant enzymes in leaves was also considered. Significant reductions in growth parameters (i.e. leaf area, biomass and shoot height), photosynthesis and chlorophyll a and b content were detected in ZYMV-infected leaves in comparison to healthy controls. Antioxidant enzyme activities were increased up to 3-fold for peroxidase (POD), 2-fold for ascorbate peroxidase (APX) and catalase (CAT) activities and 1.3-fold for SOD activity by virus infection. ZYMV infection also caused increases in H2O2 and malondialdehyde (MDA) contents. These results suggest that ZYMV infection causes oxidative stress in pumpkin leaves leading to the development of epidemiological symptoms. Interestingly, spraying pumpkin leaves with SA led to recovery from the undesirable effects of ZYMV infection. Leaves treated with 100 mM SA three days before inoculation had the appearance of healthy leaves. No distinct disease symptoms were observed on the leaves treated with 100 mM SA followed by inoculation with ZYMV. In non-infected plants, SA application increased activities of POD and superoxide dismutase (SOD) and inhibited APX and CAT activities. In contrast, SA treatment followed by ZYMV inoculation stimulated SOD activity and inhibited activities of POD, APX and CAT. In addition, MDA displayed an inverse relation, indicating inhibition of lipid peroxidation in cells under SA treatment. It is suggested that the role of SA in inducing plant defense mechanisms against ZYMV infection might have occurred through the SA-antioxidant system. Such interference might occur through inhibition or activation of some antioxidant enzymes, reduction of lipid peroxidation and induction of H2O2 accumulation following SA application.